X-Box-Binding Protein 1 Splicing Induces an Autophagic Response in Endothelial Cells: Molecular Mechanisms in ECs and Atherosclerosis

Sophia Kelaini*, Rachel Caines, Lingfang Zeng, Andriana Margariti

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Atherosclerosis is the leading cause of death in the developed world and involves the production of an atherosclerotic plaque in the artery wall, limiting blood flow and resulting in conditions such as peripheral artery disease, coronary heart disease, myocardial infarction, and stroke. Autophagy is a method of self-digestion, primarily a survival pathway for the cell, to remove and/or recycle old and damaged proteins in the cytoplasm. There is increasing evidence that autophagy takes place in severe atherosclerotic plaques implicating macrophages and vascular smooth muscle cells. In addition, oxidized low-density lipoprotein (Ox-LDL) can also trigger autophagy in endothelial cells (ECs) through LC3β/BECLIN-1, leading to the lysosome-mediated degradation of Ox-LDL. However the role of autophagy in atherosclerosis still remains shrouded in mystery, as it is still debated whether autophagy is a damaging or a protective mechanism or a balance of both is needed for normal cellular function. X-Box binding protein 1 (XBP1) mRNA splicing is involved in the regulation of autophagy in ECs through BECLIN-1 transcriptional activation. It has recently been shown that sustained activation of XBP1 results in EC apoptosis and development of atherosclerosis. More evidence has shown the importance of XBP1 in eliciting an autophagic response in ECs. Therefore, it seems that the threshold of the autophagic responses could be determined through the tight regulation of the expression and duration of splicing activation of molecules, such as XBP1s, in a cell-specific manner.

Original languageEnglish
Title of host publicationAutophagy
Subtitle of host publicationCancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging
PublisherElsevier Inc.
Pages259-268
Number of pages10
Volume11
ISBN (Electronic)9780128094273
ISBN (Print)9780128054208
DOIs
Publication statusPublished - 18 Jan 2017

Keywords

  • Atherosclerosis
  • Endothelial cell
  • Regulation
  • Splicing
  • XBP1

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)

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